AB0443 LONG-TERM OUTCOMES OF MULTITARGET THERAPY OF MYCOPHENOLATE MOFETIL AND TACROLIMUS IN LUPUS NEPHRITIS: A SINGLE CENTER RETROSPECTIVE ANALYSIS
Authors: Y. Imai, H. Ikeuchi, J. Suwa, Y. Ohishi, M. Watanabe, M. Nakasatomi, H. Hamatani, T. Sakairi, Y. Kaneko, K. Hiromura
Journal: Annals of the Rheumatic Diseases (2022)

Background Recent studies showed the efficacy of multitarget therapy with mycophenolate mofetil (MMF) and calcineurin inhibitor for induction therapy for lupus nephritis (LN) 1 . However, long-term outcomes have not been well elucidated. Objectives We retrospectively analyzed the long-term outcomes of multitarget therapy of MMF and tacrolimus. Methods We examined 27 LN patients (4 male, 23 female) treated with multitarget therapy for induction therapy between Oct. 2009 and Nov. 2018 in our department. Complete remission (CR) was defined as 1) UPCR&lt;0.5 g/gCr, and 2) serum creatinine (S-Cr) normal or if abnormal, within 15% of baseline; 1) and 2) were observed in 2 consecutive visits. Relapse was defined as UPCR&gt;1.0 g/gCr or intensification of immunosuppressive treatment after achievement of CR. Results The mean age was 38.6±11．6 years old. 17 patients were new-onset LN, and 10 patients were relapse LN. UPCR and eGFR before treatment were 4.42±2.98 g/gCr and 71.5±32.9 mL/min/1.73m 2 , respectively. Renal histology was Class III in 1, III+V in ４, IV in 12. IV+V in 9 and V in 1 by ISN/RPS 2003 classification. CR at 6 and 12 months were 59% and 74%, respectively. Patients were treated by multitarget therapy for median of 25 months (IQR, 5.5-37). Finally, 26 (96%) patients achieved CR. During multitarget therapy, there were 15 serious adverse events: deep vein thrombosis in 2, myocardial infarctions in 2, cervical intraepithelial neoplasia in 2, heart failure in 1, herpes zoster in 1, viral myocarditis in 1, cytomegalovirus gastroenteritis in 1, cholecystitis in 1, pyelonephritis in 1, bacterial enteritis in 1, sepsis in 1, and breast cancer in 1. During the median observation period of 94 months (IQR, 63-111.5) after the initiation of multitarget therapy, 1 patient died due to sudden death. No patient reached end-stage kidney disease or doubling S-Cr. 16 patients relapsed at median of 32 months (IQR,13.8-64.5) after CR; 8 patients relapsed on multitarget therapy, and 8 patients relapsed after cessation of multitarget therapy. Relapse was associated with chronic lesions in renal biopsy and normal or higher C4 levels at treatment initiation by Kaplan Meier analysis (Log-rank, P=0.006, P&lt;0.001, respectively). Conclusion Multitarget therapy effectively induced CR and maintained renal function in long-term period. However, relapse was often observed during or after withdrawal of multitarget therapy. References [1]Liu Z, Zhang H, Liu Z, et al . Multitarget therapy for induction treatment of lupus nephritis: a randomized trial. Ann Int Med 2015; 162: 18-26. Disclosure of Interests Yoichi Imai: None declared, Hidekazu Ikeuchi: None declared, Junya Suwa: None declared, Yuko Ohishi: None declared, Mitsuharu Watanabe: None declared, Masao Nakasatomi: None declared, Hiroko Hamatani: None declared, Toru Sakairi: None declared, Yoriaki Kaneko: None declared, Keiju Hiromura Speakers bureau: Chugai, Astellas., Grant/research support from: Chugai, Astellas.